Paralytic shellfish poisoning (PSP) results from a mixture of phycotoxins that bind reversibly to a receptor site on the voltage-gated sodium channel found in excitable cells. The primary clinical symptom is an acute paralytic illness. Phycotoxins or algal toxins are produced by microscopic planktonic algae. These toxins accumulate on filter feeders such as bivalves. Consumption of phycotoxin-contaminated shellfish results in six diseases in humans: PSP, amnesic shellfish poisoning (ASP), Diarrheic shellfish poisoning (DSP), neurotoxic shellfish poisoning (NSP), ciguatera poisoning (CP), and cyanobacterial poisoning (CNP).
The phycotoxins that produce PSP have a common structure of 3,4,6-trialquil tetrahydropurine. Twenty-six naturally occurring PSP have been described. These phycotoxins are non-protein, low molecular weight compounds of between 289 and 450 daltons.
The gonyautoxins (GTXs) are the most abundant PSP toxins found in shellfish extract accounting for over 80% of the total toxin content. The high toxicity of the PSP toxins is due to the reversible binding to a receptor site on the voltage-gated sodium channel on excitable cells, thus blocking the influx of sodium ions and preventing nerve and muscle cells from producing action potentials, thereby blocking neuronal transmission and causing death in mammals via respiratory arrest and cardiovascular shock. Application of small amounts of PSP toxin produces a flaccid paralysis of striated muscle for periods that are dose dependant.
The gonyautoxins of the present invention provide a local anesthetic for use in mammals either by injecting a liquid preparation or as a topical anesthetic applied to the skin of mammal.
The gonyautoxins of the present invention also provide surprising beneficial results in the treatment of a variety of ailments, which may be caused or aggravated by muscle disorders, muscle spasms or muscle action.
There remains a need for a fast acting and long lasting topical anesthetic which does not damage the skin or result in rashes, irritations, sensitization or other discomforts. There also remains a need for more effective, less invasive treatments for a variety of ailments.